This invention relates to liquid crystalline membranes.
Modern techniques of controlled drug release date back to 1964 and began with the discovery that organic molecules could diffuse through silicone rubber membranes.
Almost all controlled release systems described have a common feature: the rate of release of the drug (hereafter referred to as the "permeant") is either constant, as in the case of reservoir type devices, or decreases with time according to some known profile, as in the case of matrix type devices.
Drug delivery devices may be broadly classified into two groups--the passive reservoir and matrix type devices in which the drug diffuses through or across some kind of rate limiting barrier (hereafter referred to as a membrane) or the "active" kinds of devices such as the osmotic pumps which rely on osmotic pressure differentials to deliver drugs. Mechanical and electromechanical drug delivery systems (U.S. Pat. Nos. 3,911,911 and 3,777,748) have tended to be relatively more complex than their passive counterparts. It is evident that delivery systems of the future will be required to incorporate the pharmacological flexibility of the active delivery systems without the associated considerations of increased cost and complexity. These requirements reduce to the need for a non-mechanical valve; i.e., a variable permeability membrane.
The central feature of the problem is the permeability of the membrane system involved, and the means to trigger or regulate it by means of some external agency without serious damage to the living tissues in which the device is implanted.
Several methods to control the permeability of membranes immersed in aqueous media have been reported in the literature. Briefly, the permeability of a membrane system may be enhanced by two classes of methods: modification of membrane structure and modification of the membrane's surrounding environment.
Permeability may be controlled by means of modification of a membrane's environment relating to boundary layer effects, i.e. the "unstirred" film immediately adjacent to the membrane surface (Lakshminarayanaiah, N.; "Transport phenomena in Membranes," Academic Press, New York, N.Y.; (1969), p. 129.). Among the factors examined were the relative abundance of protons in the boundary layer (Lobel, F.; and Caplan, S. R.; Journal of Membrane Science, 6, 1980, 221-234.) thickness of the boundary layer, temperature, etc. Some authors (Pasechnik, V. A.; and Cherkasov, S.; Kolloidnyi Zhurnal, 42 (4), (1980), 748-751.) have reported an increase in the permeability of ultrafiltration membranes caused by a breakdown of water in the boundary layers, which in turn was caused by an applied electric field.
Examples of triggering by modification of membrane structure have been rather more numerous--specifically, photochemical, magnetic (Langer, R.; Proc. Natl. Acad, Sci. U.S.A., (1981), 3, 1863-1867.), thermal (Rogers, C. E.; "Controlled Release Polymeric Formulations," Plenum Press, New York, N.Y., pg. 15-25), and electrical (Grodzinsky, A. J. and Eisenberg, S. R.; Proceedings of the International Conference of Biomedical Engineering, 1980.) have been reported. Of these, only magnetic triggers have been demonstrated as potentially useful for controlled release applications.